The olfactory organ gives rise to the olfactory sensory neurons and is also thought to give rise to a group of neuroendocrine cells containing gonadotropin-releasing hormone (GnRH). The cell bodies of the olfactory sensory neurons lie in the olfactory epithelium of the nose and during development their axons grow from this peripherally located sensory structure into the central nervous system (CNS). These sensory axons create a pathway, the olfactory nerve, connecting the peripheral and central nervous system. The neuroendocrine cells containing GnRH use the olfactory pathway to gain access to the CNS. Improper development of the olfactory pathway will lead not only to loss of sense of smell, but also to loss of reproductive neuroendocrine function crucial for the development of vertebrate animals, as evidenced by Kallman's Syndrome in humans. This proposal will present and test several hypothesis central to questions in developmental biology: 1) Cranial neural crest plays an inductive role in olfactory placode formation, 2) Neuroendocrine cells containing GnRH arise from cranial neural crest and not the olfactory placode, 3) Olfactory neurons expressing the same olfactory receptor type are related by lineage. Zebrafish will e used to address these questions because of the ability to mark cells and follow them in live embryos, manipulate cells in live embryos, and examine mutant phenotypes resulting from genetic screens in order to understand cellular interactions crucial to the early development of the olfactory system and its derivatives.